A nanofluidic DNA screening device for cancer-related diagnosis and research will be developed. Point mutations and single nucleotide polymorphisms will be detected optically using fluorescent hybridization probes on a fully stretched strand of chromosomal DNA as it passes through a nanoscale tube. Array-based methods for detecting single-base differences have been demonstrated, but the fluidics method proposed here has several advantages, including immunity to coincidental sequence repeats, superior detection of rare mutations in mixed samples, and the retention of correlations between different loci on the same chromosome. Fluidics-based methods for screening genetic content have been studied before (Austin 1999), but have been limited by the methods of fluidics fabrication employed. For this device, a sacrificial layer technique for fabricating fluidics has been developed which allows precise control of complex fluid circuits with nanoscale dimensions (Turner 1998). A tube smaller than the persistence length of double-stranded DNA will prevent the molecule from folding back on itself while passing through the tube, thus eliminating the primary source of error in previous attempts to implement this method.
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